The overall aim of the Core - 9002 (Systems Neuroscience) is to provide the instrumental base for the neurobiological components of the individual projects and to develop novel methods. The use of different Alzheimer~s disease (AD)-related animal models and the development and testing of numerous treatment strategies in different species (multimodel approach) is the major focus of this core. Aged, cognitively impaired rats, rats with transections of the fimbria-fornic or the perforant pathway, and mice with specific gene defects for nerve growth factor (NGF), choline acetyltransferase (ChAT) and glutam ate receptor-2 (GluR-2) will function as experimental tools for testing different ex vivo and in vivo gene transfer interventions. 9002 will provide standardized surgical (lesioning techniques, ex vivo and in vivo gene transfer), behavioral (sensorimotor function, general activity, acoustic startle, passive avoidance, water maze, five-choice serial visual discrimination, spatial delayed nonmatch-to-sample), biochemical (ChAT activity, acetylcholine, monoamines and their metobolies, amino acids) and morphological (histochemistry, immunohistochemistry, immunofluorenscence, in situ hybridization, stereology, electron microscopy) methods. This multimethodical approach supports the individual projects and, by standardizing the various methods in multiple AD-related animal models, it will enable this program to make direct comparisons between results from each project. Finally, this standardized multimodel and multimethodical strategy will help to identify potential treatments in age-dependent cognitive dysfunction.